Recombinant hyaluronic acid-incorporated self-healing injectable hydrogels for cartilage tissue engineering: a case study on effects of molecular weight.

Cartilage injury represents a significant clinical challenge, necessitating innovative repair strategies. Self-healing injectable hydrogels are emerging as promising solutions for cartilage regeneration. However, the hydrogel with robust mechanical strength mimicking the natural cartilage and appropriate extracellular matrix production has not yet been achieved. To address this challenge, we have fabricated self-healing injectable hydrogels by combining oxidized alginate (OA) and gelatin (G) with recombinant hyaluronic acid (HA) of varying molecular weights (0.5 MDa, 1.0 MDa, and 2.0 MDa) derived from metabolically engineered Lactococcus lactis. Incorporating HA resulted in improved physicochemical, mechanical, and biological properties. The 1.0 MDa HA-incorporated hydrogel (OAGH_1.0) exhibited superior injectability and self-healing efficiency due to the balance between dynamic covalent and non-covalent interactions within the hydrogel network. The OAGH_1.0 hydrogel's enhanced shear-thinning properties aided in printing the hydrogel into a mesh-like structure using a 3D printer. The OAGH_1.0 hydrogel showed an ultimate strength of 1.2 MPa, comparable to the natural cartilage. In vitro studies confirmed that these hydrogels also fostered cell adhesion, proliferation, and collagen deposition. These results indicate that the balance between dynamic covalent and non-covalent interactions achieved in the OAGH_1.0 hydrogel will open promising avenues for advancing cartilage regeneration.